Monoamine Oxidase Inhibitors (MAOIs): A Complete Guide

Monoamine Oxidase Inhibitors (MAOIs): A Complete Guide
Mary Lucas, RN
Medically reviewed by Mary Lucas, RN Written by Our Editorial Team Last updated 7/19/2020

Monoamine oxidase inhibitors, or MAOIs, are a common type of antidepressant. MAOIs are prescribed to treat major depressive disorder (MDD, or depression), as well as several other nervous system disorders.

The first MAOI medications were introduced in the 1950s, and were widely prescribed for depression and other conditions. However, over the last few decades, use of MAOIs has declined in favor of newer antidepressants.

Today, MAOIs are only prescribed in certain circumstances. Your healthcare provider may recommend an MAOI if you’ve been diagnosed with depression or another condition and still have symptoms despite using an SSRI or other type of medication. 

Below, we’ve explained what MAOIs are and how they work to treat depression, panic disorder and other conditions. We’ve also listed some of the most common MAOI medications, risks and side effects associated with MAOIs, drug interactions and more. 

Finally, we’ve answered some of the most common questions about MAOIs, from how long they take to work to how to stop using them safely.

Monoamine Oxidase Inhibitors (MAOIs): An Overview

Monoamine oxidase inhibitors, or MAOIs, first discovered in the 1950s, are an older type of antidepressant. Although MAOIs are effective at treating depression, they’re more likely to cause severe side effects and interactions than newer antidepressants.

Today, newer classes of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) have become the standard first-line treatment for depression, with MAOIs only rarely prescribed to people with depression.

In addition to depression, some MAOIs are prescribed to treat social phobia, panic disorder and depression with unusual features (such as overeating and oversleeping). MAOIs are also used in the treatment of other diseases like Parkinson’s disease.

MAOIs are effective. However, their high risk of causing side effects means that people who use them often need to make lifestyle changes to reduce their risk of experiencing interactions, such as avoiding certain foods and medications.

How Monoamine Oxidase Inhibitors (MAOIs) Work

Like other antidepressants, MAOIs work by changing the levels of certain neurotransmitters that circulate throughout your brain and body. 

Neurotransmitters are chemicals that deliver messages to and from nerve cells, allowing these cells to communicate with each other. They’re responsible for a wide range of functions in your body, from forming and storing memories to regulating your heart and other organs.

Some neurotransmitters play a role in regulating your moods, motivation and mental state. Low levels of certain neurotransmitters, such as serotonin, dopamine and norepinephrine, are linked to depression.

MAOIs change the level of certain neurotransmitters in your body by blocking an enzyme called monoamine oxidase. 

Monoamine oxidase is responsible for breaking down several neurotransmitters. 

More specifically, monoamine oxidase is responsible for breaking down the neurotransmitters serotonin, dopamine and norepinephrine, as well as the neurotransmitter tyramine. 

By blocking the effects of monoamine oxidase, MAOIs raise the levels of serotonin, dopamine and norepinephrine in your brain, allowing these neurotransmitters to continue working on the cells that are affected by depression.

This can help to improve the symptoms of depression and, in many people, assist in long-term recovery. 

List of Monoamine Oxidase Inhibitors (MAOIs)

Several different monoamine oxidase inhibitors (MAOIs) are available, although not all are still in use as antidepressants. Here are some of the current FDA-approved MAOIs for treating depression:

  • Phenelzine. Sold under the brand name Nardil®, phenelzine is prescribed to treat depression and anxiety disorders.

  • Isocarboxazid. Sold under the brand name Marplan®, isocarboxazid is prescribed to treat depression and anxiety disorders.

  • Tranylcypromine. Sold under the brand name Parnate®, tranylcypromine is prescribed to treat depression (specifically major depressive disorder) and anxiety disorders.

  • Selegiline. Sold under the brand name Emsam®, selegiline is prescribed to treat depression. Under the brand names Zelapar® and Elepryl® selegiline is also approved by the FDA as an adjunct treatment for Parkinson’s disease. 

Using Monoamine Oxidase Inhibitors (MAOIs)

Most MAOIs come in tablet or capsule form. Depending on the specific MAOI you’re prescribed, you’ll typically need to take your medication between one and four times each day. 

For example, Nardil, a popular brand of phenelzine, is typically taken at a starting dosage of one tablet (15mg) taken three times each day. Follow the instructions provided by your healthcare provider and only take your medication exactly as prescribed. 

Some MAOIs, like selegiline (Emsam, specifically), are sold as a transdermal patch. You’ll need to apply this type of medication to your skin as instructed by your healthcare provider. 

It may take several weeks before you begin to notice the effects of your medication. If you think that your medication isn’t working the way it should, don’t adjust your dosage or stop taking it on your own — instead, talk to your healthcare provider. 

Side Effects of Monoamine Oxidase Inhibitors (MAOIs)

Compared to newer antidepressants such as SSRIs and SNRIs, MAOIs are more likely to cause certain side effects and interactions.

Common side effects of MAOIs include the following:

  • Dizziness
  • Headache
  • Drowsiness
  • Sleep disturbances, including insomnia (difficulty sleeping) and hypersomnia (excessive daytime sleepiness)
  • Fatigue
  • Weakness
  • Tremors
  • Twitching
  • Myoclonic movements (sudden, involuntary jerking of muscles)
  • Hyperreflexia (overactive or overly responsive reflexes)
  • Constipation
  • Dry mouth
  • Gastrointestinal disturbances
  • Elevated levels of liver enzymes
  • Weight gain
  • Postural hypotension (drop in blood pressure upon standing)
  • Edema (swelling)
  • Sexual disturbances, such as difficulty ejaculating, erectile dysfunction and anorgasmia

Monoamine Oxidase Inhibitors (MAOIs) Safety

MAOIs are more likely to cause certain side effects than newer antidepressants. They can also interact with other medications, as well as certain foods and beverages. If you’re prescribed any type of MAOI, it’s important to be aware of the following safety issues:

  • Drug interactions. MAOIs can interact with other medications, including other styles of antidepressants, as well as some pain and allergy medications, and even herbal supplements. Some drug interactions involving MAOIs can be severe and potentially dangerous.

    If you’re prescribed an MAOI, check with your healthcare provider before using any other prescription or over-the-counter medications, supplements or herbal products.

  • Food interactions. MAOIs can interact with foods that contain tyramine and cause a dangerous increase in blood pressure. You’ll need to avoid certain foods while you’re using this type of medication.

    Your healthcare provider will provide a list of foods to avoid while you’re using any type of MAOI to treat depression or another condition.
  • Drink interactions. MAOIs can interact with certain drinks, such as beer, certain types of wine and others that contain levels of tyramine. Make sure to talk to your healthcare provider about which drinks are safe and which are to be avoided while you’re using this type of medication.
  • Pregnancy. Some antidepressants, including MAOIs, may be unsafe for women who are pregnant or breastfeeding. If your partner currently uses antidepressants, make sure they talk to their healthcare provider about safety during pregnancy and breastfeeding.
  • Serotonin syndrome. Although it’s uncommon, MAOIs can cause serotonin syndrome when used with other medications or supplements that affect the level of serotonin in the body.

    If you’re currently prescribed any MAOI or other antidepressant, make sure to check with your healthcare provider before using other medications, herbal products and/or supplements.
  • Withdrawal symptoms. Like other antidepressants, stopping MAOIs abruptly may lead to withdrawal symptoms. We’ve provided more information about this further down.

FDA “Black Box” Warning for Antidepressants

As with other antidepressants, MAOIs carry a “black box” warning from the FDA regarding an increased risk of suicidal thoughts or behavior in children, teenagers and young adults.

This warning applies to people aged 24 and under, who may have an elevated risk of suicidal thoughts or behavior while using antidepressants. If you experience any suicidal thoughts or change in mood while using any type of MAOI, seek immediate medical assistance.

Other Medications for Treating Depression

Today, MAOIs are rarely prescribed as a first-line treatment for depression due to their high risk of side effects and/or interactions. Instead, most cases of depression are treated with SSRIs or SNRIs, which are effective and less likely to produce side effects. 

Your healthcare provider may prescribe an MAOI if other antidepressants haven’t helped to treat your depression. 

We’ve listed and provided more information about other antidepressants in our complete guide to medications for depression. 

Frequently Asked Questions About MAOIs

How Long Do MAOIs Take to Work?

Like other antidepressants, MAOIs can often take several weeks to start working. For example, it can take four weeks or longer before you begin to notice the full benefits of phenelzine, one of several commonly used monoamine oxidase inhibitors.

If you’re prescribed any type of antidepressant, make sure that you continue using it even if you don’t notice any improvement during the first few weeks. If you don’t think that the medication is working, talk to your healthcare provider before making any changes to your usage. 

What Foods Should You Avoid While Using an MAOI?

MAOIs prevent your body from breaking down tyramine — a naturally occurring trace amine that can be found in certain foods and drinks.

If you’re prescribed a MAOI, consuming foods or drinks that contain tyramine may cause you to develop an excessively high serum tyramine level. This can cause a sudden increase in blood pressure that may be dangerous or, in some cases, even deadly.

To use an MAOI safely, your healthcare provider will advise you to avoid foods that contain large amounts of tyramine. Make sure not to consume the following foods or drinks at the same time as you use any type of MAOI medication:

  • Cheese. Many cheeses contain tyramine. Avoid eating cheese while you’re prescribed any type of MAOI medication. Cheeses with a strong taste or aged cheeses are usually the highest in tyramine and most likely to interact with MAOIs. Cheeses made with pasteurized milk may be safe for you to consume. However, make sure to check with your healthcare provider first.

  • Dried, cured, smoked or processed meats, including any meats treated with salt and nitrate, as well as smoked or processed meats. Any meats prepared using tenderizers should also be avoided.
  • Dried and/or overripe fruits, including prunes, raisins, as well as overripe avocados and bananas.
  • Fermented or pickled foods, such as sauerkraut, pickles, kimchi and tofu.
  • Sauces, such as fish sauce, miso, teriyaki sauce, soy sauce and shrimp sauce.
  • Spreads and breads containing yeast extract, such as brewer’s yeast, Marmite and sourdough bread.
  • Alcoholic drinks, including red wine, fortified wine, beer and certain liqueurs.
  • Soy products and soybeans.
  • Broad beans (fava beans) and snow peas.
  • Spoiled foods.

If you’re prescribed an MAOI, make sure to ask your healthcare provider for a full list of foods to avoid while you take your medication. Your healthcare provider should also provide you with information on what to do if you accidentally consume an unsafe fruit or drink. 

Do MAOIs Cause Weight Gain?

Antidepressants are commonly associated with weight gain. Although the link is smaller than many people think, some antidepressants may cause a small amount of weight gain over the long term.

In one scientific review, researchers found that phenelzine was the MAOI most likely to cause weight gain, while other MAOIs, such as isocarboxazid and tranylcypromine, were either less associated with weight gain or had no association with weight gain at all.

Some experts also believe that MAOIs are less likely to cause weight gain than other types of antidepressants, such as tricyclic antidepressants.

How Can You Safely Stop Taking MAOIs?

Like other antidepressants, MAOIs can cause withdrawal symptoms if you abruptly stop using them as prescribed.

Withdrawal symptoms, referred to as antidepressant discontinuation syndrome, affect about 20 percent of people who stop taking antidepressants without tapering their dosage gradually over time.

If you’re prescribed an MAOI and suddenly stop taking it, you may experience difficulty sleeping, nausea, sensory disturbances, hyperarousal and flu-like symptoms. In some cases, withdrawal symptoms from antidepressants can be severe enough to require hospitalization.

If you no longer want to use an MAOI to treat depression, or feel that you don’t need medication anymore, talk to your healthcare provider before making any changes. Your healthcare provider may advise you to reduce your dosage gradually over time to avoid or minimize any withdrawal-related side effects. 

Can You Drink Alcohol While Using MAOIs?

Using alcohol with MAOIs is not recommended. The FDA label for Nardil, a brand of the MAOI phenelzine, specifically cautions that the medication should not be used with central nervous system depressants such as alcohol.

Similar warnings can be found in FDA documentation for the medications Marplan® (a common brand of the MAOI isocarboxazid) and Parnate® (a brand of the MAOI tranylcypromine).

Using alcohol with antidepressants, including MAOIs, can increase your risk of side effects. As many alcoholic beverages contain tyramine, drinking while using MAOIs also increases your risk of experiencing potentially serious interactions and increases in blood pressure.

To stay safe, it’s best to avoid drinking alcohol while you’re undergoing treatment with MAOIs or other antidepressants. If you drink alcohol often, or have an alcohol use disorder, make sure to talk to your healthcare provider before you start taking any type of antidepressant. 

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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.